尼古丁戒断综合征的性别差异及其神经生物学机制

Gender-Dependent Effects and Neurobiological Mechanisms in Nicotine Withdrawal Syndrome

摘要: 烟草成瘾至今仍是世界上许多国家主要的可预防的死亡和残疾原因，而尼古丁戒断症状是成瘾后戒烟率低，复吸率高的重要原因。本文将回顾尼古丁戒断症状在行为表现上的性别差异，并从激素和神经递质系统两个层面来分析这种性别差异的神经生物学机制。综合实验研究发现了，女性通常比男性有更严重的戒断症状，更难以戒烟，而戒烟后产生更强烈的焦虑或抑郁情绪是女性更容易复吸的重要原因。从激素层面上分析，女性的HPA轴对环境变化更加敏感，戒断会引起更大强度的应答，使得女性的焦虑程度更重，也更容易感受到压力而复吸；此外孕酮可能会在一定程度上缓解戒断后HPA轴激素增加引起的焦虑情绪，而雌二醇的增加会加重负面情绪，所以推测女性在生殖周期中的卵泡期复吸的可能性更大。从递质系统水平分析，发现烟碱乙酰胆碱受体(nACHRs) β2亚基主要促进了男性中尼古丁戒断症状的形成，α5亚基主要在女性的尼古丁戒断中起抑制作用；而多巴胺系统在其中的调控作用更加复杂。文献研究表明，将性别作为尼古丁戒断症状研究中的一个因素将提高我们在个性化戒烟项目中的成功率。

Abstract: Tobacco addiction remains a major cause of preventable death and disability in many countries of the world, and nicotine withdrawal syndrome is important reason for low rate of smoking cessation and high rate of relapse. This paper will review the sex differences in behavioral manifestations of nicotine withdrawal syndrome and analyze the neurobiological mechanisms of this gender difference from the perspectives of hormone and neurotransmitter systems. A combination of experimental studies has found that women tend to have more severe withdrawal symptoms than men and are less likely to quit smoking, and that higher levels of anxiety or depression after quitting smoking may explain why women are more likely to relapse. From the perspective of hormones, women's HPA axis is more sensitive to environmental changes. Withdrawal will cause a stronger response, which makes women more anxious and more likely to feel pressure and relapse. In addition, progesterone may relieve the anxiety caused by the increase of HPA axis hormone after withdrawal to a certain extent, while the increase of estradiol will aggravate the negative emotions, so women are more likely to relapse during the follicular phase of the reproductive cycle. At the transmitter system level, the nicotinic acetylcholine receptor (nACHRs) 2 subunit was found to promote nicotine withdrawal symptoms in males, and the 5 subunit was found to inhibit nicotine withdrawal in females. The role of the dopamine system is more complex. The literature suggests that using gender as a factor in nicotine withdrawal symptoms research will improve our success rate in personalized cessation programs.